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United States Environmental Protection Agency

Office of Water Regulations and Standards Criteria and Standards Division Washington DC 20460

EPA 440 5-80-042 October 1980

EPA Ambient Water Quality Criteria for 2,4-dichlorophenol

AMBIENT WATER QUALITY CRITERIA FOR

2,4-DICHLOROPHENOL

Prepared By U.S. ENVIRONMENTAL PROTECTION AGENCY

Office of Water Regulations and Standards Criteria and Standards Division

Washington, D.C.

Office of Research and Development Environmental Criteria and Assessment Office

Cincinnati, Ohio

Carcinogen Assessment Group Washington, D.C.

Environmental Research Laboratories Corvalis, Oregon Duluth, Minnesota

Gulf Breeze, Florida Narragansett, Rhode Island

DISCLAIMER

This report has been reviewed by the Environmental Criteria and

Assessment Office, U.S. Environmental Protection Agency, and approved

for publication. Mention of trade names or commercial products does not

constitute endorsement or recommendation for use.

AVAILABILITY NOTICE

This document is available to the public through the National

Technical Information Service, (NTIS), Springfield, Virginia 22161.

ii

FOREWORD

Section 304 (a)(1) of the Clean Water Act of 1977 (P.L. 95-217), requires the Administrator of the Environmental Protection Agency to publish criteria for water quality accurately reflecting the latest scientific knowledge on the kind and extent of all identifiable effects on health and welfare which may be expected from the presence of pollutants in any body of water, including ground water. Proposed water quality criteria for the 65 toxic pollutants listed under section 307 (a)(1) of the Clean Water Act were developed and a notice of their availability was published for public comment on March 15, 1979 (44 FR 15926), July 25, 1979 (44 FR 43660), and October 1, 1979 (44 FR 56628). This document is a revision of those proposed criteria based upon a consideration of comments received from other federal Agencies, State agencies, special interest groups, and individual scientists. The criteria contained in this document replace any previously published EPA criteria for the 65 pollutants. This criterion document is also published in satisifaction of paragraph 11 of the Settlement Agreement in Natural Resources Defense Council, et. al, vs. Train, 8 ERC 2120 (D.D.C. 1976), modified, 12 ERC 1833 (D.D.C. 1979).

The term "water quality criteria" is used in two sections of the Clean Water Act, section 304 (a)(1) and section 303 (c)(2). The term has a different program impact in each section. In section 304, the term represents a non-regulatory, scientific assessment of ecological ef- fects. The criteria presented in this publication are such scientific assessments. Such water quality criteria associated with specific stream uses when adopted as State water quality standards under section 303 become enforceable maximum acceptable levels of a pollutant in ambient waters. The water quality criteria adopted in the State water quality standards could have the same numerical limits as the criteria developed under section 304. However, in many situations States may want to adjust water quality criteria developed under section 304 to reflect local environmental conditions and human exposure patterns before incorporation into water quality standards. It is not until their adoption as part of the State water quality standards that the criteria become regulatory.

Guidelines to assist the States in the modification of criteria presented in this document, in the development of water quality standards, and in other water-related programs of this Agency, are being developed by EPA.

STEVEN SCHATZOW Deputy Assistant Administrator Office of Water Regulations and Standards

iii

CRITERIA

CRITERIA DOCUMENT

2,4-DICHLOROPHENOL

Aquatic Life

The available data for 2,4-dichlorophenol indicate that acute and chron-

ic toxicity to freshwater aquatic life occur at concentrations as low as

2,020 and 365 µg/l, respectively, and would occur at lower concentrations

among species that are more sensitive than those tested. Mortality to early

life stages of one species of fish occurs at concentrations as low as 70

µg/l.

Only one test has been conducted with saltwater organisms and 2,4-di-

chlorophenol and no statement can be made concerning acute or chronic tox-

icity.

Human Health

For comparison purposes, two approaches were used to derive criterion

levels for 2,4-dichlorophenol. Based on available toxicity data, for the

protection of public health, the derived level is 3.09 mg/l. Using avail-

able organoleptic data, for controlling undesirable taste and odor qualities

of ambient water, the estimated level is 0.3 µg/l. It should be recognized

that organoleptic data as a basis for establishing a water quality criterion

have limitations and have no demonstrated relationship to potential adverse

human health effects.

vi

TABLE OF CONTENTS

Page

Criteria Summary

Introduction

Aquatic Life Toxicology Introduction Effects

Acute Toxicity Chronic Toxicity Plant Effects Residues Miscellaneous Summary

Criterion References

Mammalian Toxicology and Human Health Effects Exposure

Ingestion from Water Ingestion from Food Inhalation Dermal

Pharmacokinetics Absorption Distribution Metabolism Excretion

Effects Acute, Subacute and Chronic Toxicity Synergism and/or Antagonism Teratogenicity Mutagenicity Carcinogenicity Other Effects

Criterion Formulation Current Levels of Exposure Special Groups at Risk Basis and Derivation of Criterion

References

A-1

B-1 B-1 B-2 B-2 B-3 B-3 B-4 B-4 B-5 B-5 B-7

C-1 C-1 C-1 C-9 C-16 C-16 C-17 C-17 C-17 C-17 C-19 C-19 C-19 C-23 C-24 C-24 C-24 C-29 C-31 C-31 C-31 C-31 C-35

v

ACKNOWLEDGEMENTS

Aquatic Life Toxicity:

William A. Brungs, ERL-Narragansett U.S. Environmental Protection Agency

Mammalian Toxicology and Human Health Effects:

Gary Osweiler (author) University of Missouri

John F. Risher (doc. mgr.) ECAO-Cin U.S. Environmental Protection Agency

Bonnie Smith (doc. mgr.) ECAO-Cin U.S. Environmental Protection Agency

A. Wallace Hayes University of Mississippi Medical Center

Steven D. Lutkenhoff, ECAO-Cin U.S. Environmental Protection Agency

Jerry F. Stara, ECAO-Cin U.S. Environmental Protection Agency

Philip J. Wirdzek, OWPS U.S. Environmental Protection Agency

David J. Hansen, EEL-Gulf Breeze U.S. Environmental Protection Agency

Herbert Cornish University of Michigan

Patrick Durkin Syracuse Research Corporation

Terence M. Grady, ECAO-Cin U.S. Environmental Protection Agency

Van Kozak University of Wisconsin

Herbert Schumacher National Center for Toxicological Research

William W. Sutton, EMSL-LV U.S. Environmental Protection Agency

Gunther Zweig, OPP U.S. Environmental Protection Agency

Technical Support Services Staff: D.J. Reisman, M.A. Garlough, B.L. Zwayer, P.A. Daunt, K.S. Edwards, T.A. Scandura, A.T. Pressley, C.A. Cooper, M.M. Denessen.

Clerical Staff: C.A. Haynes, S.J. Faehr, L.A. Wade, D. Jones, B.J. Bordicks, B.J. Quesnell, C. Russom, R. Rubinstein.

iv

2,4-Dichlorophenol (2,4-DCP is a commercially produced substituted

phenol used entirely in the manufacture of industrial and agricultural prod-

ucts. As an intermediate in the chemical industry, 2,4-DCP is utilized

principally as the feedstock for the manufacture of the herbicide, 2,4-di-

chlorophenoxyacetic acid (2,4-D), 2,4-D derivatives (germicides, soil steri-

lants, etc.) and certain methyl compounds used in mothproofing, antiseptics,

and seed disinfectants. 2,4-DCP is also reacted with benzene sulfonyl chlo-

ride to produce miticides or further chlorinated to pentachlorophenol, a

wood preservative (U.S. EPA, 1975).

INTRODUCTION

2,4-Dichlorophenol is a colorless, crystalline solid having the empiri-

cal formula C6H4Cl2O, a molecular weight of 163.0 (Weast, 1975), a

density of 1.383 at 60°F/25°C and a vapor pressure of 1.0 mm Hg at 53.0°C

(Sax, 1975). The melting point of 2,4-DCP is 45°C, and the boiling point is

210°C at 760 mm Hg (Aly and Faust, 1965; Weast, 1975).

2,4-DCP is slightly soluble in water at neutral pH and dissolves readily

in ethanol and benzene (Kirk and Othmer, 1964). 2,4-DCP behaves as a weak

acid and is highly soluble in alkaline solutions, since it readily forms the

corresponding alkaline salt. The dissociation constant (pKa) for 2,4-DCP

has been reported to be 7.48 (Pearce and Simpkins, 1968). Unlike the mono-

chlorophenols, 2,4-DCP is not volatile from aqueous alkaline solutions (Kirk

and Othmer, 1964).

2,4-DCP is readily prepared without benefit of a catalyst using gaseous

chlorine and molten phenol at 80 to 100°C. Synthesis is also attainable

through the chlorination of the monochlorophenols (Kirk and Othmer, 1972).

A-1

It has been demonstrated that phenol is quite reactive to chlorine in

dilute aqueous solutions over a wide pH range (Carlson and Caple, 1975; Mid-

daugh and Davis, 1976).

Although 2,4-DCP presently has no direct commercial application, it is

used as an important chemical intermediate, and it is synthesized from

dilute aqueous solutions. Its identification as a metabolic intermediate

and degradation product of various commercial products by plants (Kirk and

Othmer, 1972), microorganisms (Kearney and Kaufman, 1972; Steenson and

Walker, 1957; Bell, 1957, 1960; Evans and Smith, 1954; Fernley and Evans,

1959; Loos, et al. 1967a,b; Loos, 1969) and sunlight (Aly and Faust, 1964;

Crosby and Tutass, 1966; Mitchell, 1961) has been well established.

Numerous studies on the microbial degradation of 2,4-DCP have been con-

ducted, revealing degradation to yield succinic acid (Alexander and Aleem,

1961; Macrae, et al. 1963; Paris and Lewis, 1973; Fernley and Evans, 1959;

Bell, 1957, 1960; Bollag, et al. 1968a,b; Macrae and Alexander, 1965; Chu

and Kirsch, 1972; Ingols, et al. 1966; Chapman, 1972; Duxbury, et al. 1970;

Loos, et al. 1967b; Tiedje, et al. 1969).

Few data exist regarding the persistence of 2,4-DCP in the environment.

2,4-DCP is slightly soluble in water, while its alkaline salts are readily

soluble in aqueous solutions. Its low vapor pressure and non-volatility

from alkaline solutions would cause it to be only slowly removed from sur-

face water via volatilization. Studies have indicated low sorption of

2,4-DCP from natural surface waters by various clays (Aly and Faust, 1964).

A-2

REFERENCES

Alexander, M. and M.J.H. Aleem. 1961. Effect of chemical structure on

microbial decomposition of aromatic herbicides. Jour. Agric. Food Chem.

9: 44.

Aly, O.M. and S.D. Faust. 1964. Removal of 2,4-dichlorophenoxyacetic acid

and derivatives from natural waters. Jour. Am. Water Works Assoc. 57: 221.

Bell, G.R. 1957. Morphological and biochemical characteristics of a soil

bacterium which decomposes 2,4-dichlorophenoxyacetic acid. Can. Jour.

Microoiol. 3: 821.

Bell, G.R. 1960. Studies on a soil Achromobacter which degrades 2,4-di-

chlorophenoxyacetic acid. Can. Jour. Microbial. 6: 325.

Bollag, J.M., et al. 1968a. 2,4-D metabolism: Enzymatic hydroxylation of

chlorinated phenols. Jour. Agric. Food Chem. 16: 826.

Bollag, J.M., et al. 1968b. Enzymatic degradation of cnlorocatechols.

Jour. Agric. Food Chem. 16: 829.

Carlson, R.14. and R. Caple. 1975. Organo-chemical Implications of Water of

Water Chlorination. In: Proc. Conf. Environ. Impact Water Chlorination.

p. 73.

4-3

Chapman, P.J. 1972. An Outline of Reaction Sequences Used for the Bacteri-

al Degradation of Phenolic Compounas. In-: Degraaation of Synthetic Organic

Molecules in the Biosphere. Proc. Conf. Natl. Acaa. Sci., Washington, D.C.

p. 17.

Chu, J.P. and E.J. Kirsch. 1972. Metabolism of PCP by axenic bacterial

culture. Appl. Microbial. 23: 1033.

Crosby, D.G. and H.O. Tutass. 1966. Photodecomposition of 2,4-dichloro-

phenoxyacetic acid. Jour. Agric. Fooa Chem. 14: 596.

Duxbury, J.M., et al. 1970. 2,4-D metabolism: enzmatic conversion of ch'lo-

romaleylacetic Kid to succinic acid. Agric. Food. Chem. 18: 199.

Evans, W.C. and B. Smith. 1954. The photochemical inactivation and micro-

bial metabolism of the chlorophenoxyacetic acid herbicides. Proc. Biochem.

sot. 571.

Fernley, H.N. and W.C. Evans. 1959. Metaoolism of 2,4-dichlorophenoxy-

acetic acid by soil pseudomonas. Proc. Biochem. Sot. 73: 228.

logical activity of halopheno Ingols, R.S., et al. 1966. Bio

Water Pollut. Control Fed. 38: 629.

1s. Jour.

Kearney, P.C. and D.N. Kaufman. 1972. MicroDial Degradation of Some Chlo-

rinated Pesticides. In: Degradation of Synthetic Organic Molecules in the -

Biosphere. Proc. Conf. Natl. Acad. Sci., Washington, D.C. p.166.

A-4

Kirk, R.E. ana D.F. Othmer. 1964. Kirk-Othmer Encyclopedia of Cnemical

Technology. 2nd ed. Interscience Publisners, New York.

ia of Chem Kirk, R.E. and D.F. Othmer. 1972. Kirk-Othmer Encycloped

Technology. 3rd ed. Interscience Publishers, New York.

Loos, M.A. 1969.

0.0. Kaufman (eds.

Phenoxyalkanoic Acias. Part I.

), Degradation of Herbiciaes. Marce

In: P.C. Kearney -

1 Dekker, New York.

ical

and

Loos, M.A., et al. 1967a. Formation of 2,4-dichlorophenol and 2,4-di-

chloroanisole from 2,4-D by Arthrobacter sp. Can. Jour. Microbial. 13: 691.

Loos, M.H., et al. 1967b. Phenoxyacetate herbicide detoxication by bacte-

rial enzymes. Jour. Agric. Fooa. Chem. 15: 858.

Macrae, I.C. and M. Alexander. 1965. Microoial degradation of selected

pesticides in soil. Jour. Agric. Food Chem. 13: 72.

Macrae, I.C., et al. 1963. The decomposition of 4-(2,4-dichlorophenoxy-

butyric) acid by Flavobacterium sp. Jour. Gen. Microbial. 32: 69.

Midaaugh, D.P. and W.P. Davis. 1976. Impact of Chlorination Processes on

Marine Ecosystems. In: Water Quality Criteria Research of tne U.S. Environ.

Prot. Agency. EPA Report No. 600/3/-76-079. Presented at 26th Annu. Meet.

Am. Inst. Biol. Sci., August 1975.

A-5

Mitchell, L.C. 1961. The effect of ultraviolet light (2537A) on 141 pesti-

cide chemicals by paper chromatography. Jour. Off. Analyt. Chem. 44: 643.

Paris, D.F. and D.L. Lewis. 1973. Chemical and microbial degradation of 10

selected pesticides in aquatic systems. Residur Rev. 45: 95.

Pearce, P.J. and R.J.J. Simpkins. 1968. Acid strengths of some picric

acids. Can. Jour. Chem. 46: 241.

Sax, N.I. 1975. Dangerous properties of industrial materials. 4th ed.

Van Nostrand Rheinold Co., New York.

Steenson, T.I. and N. Walker. 1957. The pathway of breakdown of 2,4-di-

chloro- and 4-chloro-2-methyphenoxyacetate by bacteria. Jour. Gen. Micro-

biol. 16: 146.

Tiedje, J. M., et al. 1969. 2,4-D metabolism: pathway of degradation of

chlorocatechols by Arthrobacter sp. Jour. Agric. Food Chem. 17: 1021.

U.S. EPA. 1975. Significant organic products and organic chemical manufac-

turing. Washington, D.C.

Weast, R.D., (ed.) 1975. Handbook of Chemistry and Physics. 55th ed. CRC

Press, Cleveland, Ohio.

A-6

Aquatic Life Toxicology*

INTRODUCTION

2,4-Dichlorophenol has been widely used as a chemical intermediate in

the manufacture of herbicides, germicides, temporary soil sterilants, plant

growth regulators, mothproofing agents, seed disinfectants, miticides, and

wood preservatives. In spite of this, there are only limited toxicity data

available dealing with effects of 2,4-dichlorophenol on freshwater aquatic

organisms. Flavor-impairment studies with 2,4-dichlorophenol showed that

flesh tainting in fish occurred at substantially lower concentrations than

those that produced other adverse effects on plant, fish, and invertebrate

species. For this reason, flavor-impairment information may be an important

consideration in deriving the 2,4-dichlorophenol criterion for freshwater

aquatic organisms. Additional testing of 2,4-dichlorophenol is necessary to

meet the minimum data base requirement, detailed in the guidelines, for the

derivation of a criterion. This testing should verify if flavor-impairment

of fish flesh is, indeed, the most sensitive and important parameter for

protecting the presence of and the uses of freshwater aquatic organisms.

Only one test has been conducted with 2,4-dichlorophenol and saltwater

organisms.

*The reader is referred to the Guidelines for Deriving Water Quality Cri- teria for the Protection of Aquatic Life and Its Uses in order to better understand the following discussion and recommendation. The following tables contain the appropriate data that were found in the literature, and at the bottom of each table are calculations for deriving various measures of toxicity as described in the Guidelines.

B-1

conducted using flow-through conditions and measured concentrations.

Phipps, et al. (Manuscript) calculated a 96-hour LC50 of 8,230 µg/l for

fathead minnows. This is more than 4 times higher than the 96-hour LC50

nia magna with that of other invertebrate species.

Only two acute values dealing with 2,4-dichlorophenol effects on fresh-

water fish species were available (Table 1) and only one of these tests was

of 2,020 µg/l for bluegills determined under static test conditions using

nominal concentrations (U.S. EPA, 1978). Although differences in test meth-

ods make comparisons difficult, it appears bluegills may be slightly more

sensitive to 2,4-dichlorophenol than are fathead minnows.

The LC50 values for Daphnia magna fall between the LC50 values found

for bluegills and fathead minnows. From the few acute data available, it

appears that there are no large differences in the sensitivity of fish and

invertebrate species to 2,4-dichlorophenol,

The 96-hour LC50 values for chlorinated phenols and bluegills (U.S.

EPA, 1978) in this and other criterion documents are directly related to the

degree of chlorination. These values decrease from 6,590 µg/l for 2-chloro-

phenol and 3,830 µg/l for 4-chlorophenol to 60 and 70 µg/l for pentachlo-

The data base for freshwater invertebrate species (Table 1) consists of

two static tests on a single cladoceran species. The 48-hour LC50 values

determined for Daphnia magna by Kopperman, et al. (1974) and U.S. EPA (1978)

were 2,610 µg/l and 2,600 µg/l, respectively. The LC50 values from both

tests show good reproducibility of results between investigators. Since all

the invertebrate acute data available for 2,4-dichlorophenol are for only

one species, it is impossible to determine the relative sensitivity of Daph-

EFFECTS

Acute Toxicity

B-2

rophenol. Data for other species do not correlate as well.

Chronic Toxicity

The freshwater chronic data base for 2,4-dichlorophenol consists of a

single embryo-larval test (Holcombe, et al. Manuscript) conducted with fat-

head minnows. The chronic limits determined from this study (290-460 pg/l)

were based on effects on larval survival, and the resulting chronic value

was 365 ug/l (Table 2).

There appears to be a moderate difference between the concentration of

2,4-dichlorophenol that cause acute and chronic effects on fathead minnows.

The acute-chronic ratio for this species is 23 (Table 2).

Data from an embryo exposure and an additional 4-day larval exposure

with three species of fishes at two water hardnesses (Birge, et al. 1979)

will be discussed in the miscellaneous section.

Species mean acute and chronic values for 2,4-dichlorophenol are listed

in Table 3.

Plant Effects

The toxicity of 2,4-dichlorophenol to freshwater aquatic plants does not

appear important in the derivation of a criterion since deleterious on

plants (Table 4) occurred only at much higher concentrations than those

which produced acute toxic effects on fish and invertebrate species. How-

ever, the knowledge that 2,4-dichlorophenol is not highly toxic to plants is

important because 2,4-dichlorophenol is used in producing the commonly used

herbicide, 2,4-D (2,4-dichlorophenoxyacetic acid). Some observed toxic ef-

fects of 2,4-dichlorophenol on plants were the complete destruction of chlo-

rophyll in Chlorella pyrenoidosa at 100,000 ug/l (Huang and Gloyna, 1968)

and a 50 percent reduction in chlorophyll in Lemna minor at 58,320 vg/l --

(Blackman, et al. 1955). Huang and Gloyna (1968) also determined that there

B-3

was a 56.4 percent reduction of photosynthetic oxygen production in Chlor-

ella pyrenoidosa after exposure to 50,000 pg/l for 120 minutes.

Residues

No measured steady-state bioconcentration factor (BCF) is available for

2,4-dichlorophenol.

Miscellaneous

Birge, et al. (1979) determined LC50 values for three fish species

after embryo exposures and after additional 4-day larval exposures at hard-

nesses of 50 and 200 mg/l as CaC03 [Table 5). The LC50 values after the

B-day larval exposures were 80 and 70 ug/l for rainbow trout, 390 and 260

pg/l for goldfish, and 1,350 and 1,070 ugll for channel catfish at hard-

nesses does not substantially affect toxicity, although for all species

tested the LCso values for 2,4-dichlorophenol were slightly higher at low

hardness than at high hardness. The LC50 value of 260 ug/l for goldfish

(Birge, et al. 1979), which was based on an 8-hour total exposure of embryos

and larvae, was considered to be the lowest freshwater acute value for

2,4-dichlorophenol. Rainbow trout embryos and larvae exposed in this study

were fathead minnows since the chronic value for fatheads is 365 pg/l

(Holcombe, et al. Manuscript). Since the rainbow trout LC50 of 70 ,,g/l

(Birge, et al. 1979) was based on a relatively long-term study (24-day em-

bryo exposure plus a 4-day larval exposure), this value was considered to be

the lowest chronic value.

Flavor-impairment studies (Shumway and Palensky, 1973) showed that flesh

tainting occurred when 2,4-dichlorophenol concentrations ranging from 0.4

llgll to 14 vgll, depending on the species of fish tested, were exceeded

(Table 5). Based on the available data for 2,4-dichlorophenol, flavor-

impairment in fish occurs at lower concentrations than other effects used to

B-4

evaluate toxicity and may be an important consideration in deriving a cri-

terion. Since the purpose of the Guidelines is to set water quality cri-

teria which protect both the presence and uses of aquatic life, a criterion

which will protect against tainting of fish flesh is necessary to preserve

the quality of the freshwater fishery. However, the lack of toxicity data

for 2,4-dichlorophenol makes it impossible to ascertain if a criterion based

on flavor-impairment of fish flesh would be low enough to protect all fresh-

water aquatic organisms.

The only saltwater data available on the effects of 2,4-dichlorophenol

are from an acute exposure to mountain bass, a species endemic in Hawaii

(Hiatt, et al. 1953). Abnormal behavioral responses, including rapid swim-

ming in a vertical position, gulping at the surface of the water, and jerky

motions, were observed in a nominal concentration of 20,000 pg/l.

Summary

Acute effects on freshwater fish and invertebrate species were observed

at concentrations from 260 to 8,230 pg/l. The chronic value for the fathead

minnow was 365 11911 with an acute-chronic ratio of 23. An embryo and 4-day

larval exposure of rainbow trout yielded an LC50 value of 70 ,,g/l. The

lowest plant effect (50,000 ug/l) caused by exposure to 2,4-dichlorophenol

was based on a reduction in photosynthetic oxygen production in an algal

species. Effects on flavor-impairment of largemouth bass occurred when con-

centrations of 2,4-dichlorophenol exceeded 0.4 ug/l.

CRITERIA

The available data for 2,4-dichlorophenol indicate that acute and

chronic toxicity to freshwater aquatic life occur at concentrations as low

as 2,020 and 365 pg/l, respectively, and would occur at lower concentrations

among species that are more sensitive than those tested. Mortality to early

B-5

life stages of one species of fish occurs at concentrations as low as 70

vgll*

Only one test has been conducted with saltwater organisms and 2,4-di-

chlorophenol, and no statement can be made concerning acute or chronic

toxicity.

8-6

spmccles

Table 1. Acute values far 2,+dlchlorophewl

Species Mean Lc5o/Ec5o Acute Valw

uetbod* (w/l 1 Qws/l)

FRESHWATER SPECIES

C ladoceran, maqna Daphn I a

C ladoceran, Daphnia magna

s, u 2,610

s, u 2,600 2,605

Fathead mlnnou (juvenile), Fl, H Pimephales prcmelas

8,230 8,230

Eluegl I I, macrochlrus Lepanis

s, u 2,020 2,020

Reference

Kopperman, et al. 1974

U.S. EPA, 1978

Phlpps, et al. Hanuscr ipt

U.S. EPA, 1978

* S 9 stat Ic, Ff = f low-through, U = unmeasured, M = measured

No Flnal Acute Values are calculable since the minlrwm data base requirements are not met.

B-7

Table 2. Chrcmlc values for 2,4-dichkrophuwf WolaMe, at al. JWwcrlpt)

Species Mean Llalts Chronic Vslrn

SPOCJSr nethoe (rs/l) (cg/I I

FRESHWATER SPECIES

Fathead minnow, Plawphales prcmelas

ELS 290-460 365

* ELS = early I Ife stage

Acuttihronlc Ratlo

Species

Fathead atl~now, Plrnephales promelas

Chronic Acute Value Value (WI/l) (L&l/ I)

365 8,230

Ratio

23

B-8

Table 3. Spocles mean acute and chronic values

Species Mum Acute Valud

NUB& SpoCleS (&I,

FRESHWATER SPEClES

3 Fathead minnow, 8,230 Plmephales prcmelas

2 C ladoceran, 2,605 Oaphn la nagna

I f3luegll I, 2,020 macrochlrus Lepomls

for 2,4-dlch loro@enol

spoclos Mwul Cbronlc Value Acute-chronic

(rs/l) Ratio**

365 23

l Rank from high concentration to low concentration & species mean acute value.

*“see the Guldellnes for derlvatlon of thls ratlo.

B-9

Table 4. Plant values for 2,4-dlchlwophmol

Result Species Effect cl4/r) Ref orenob

FRESHWATER SPEC I ES

A f9a, Chlorella pyrenoldosa

Complete destruct ion of ch lorophy I I

100,000 Ihang 6 Gloyna, 1968

Alga, Chlorella pyrenoldosa

56. S$ redud ion 50,000 hang b. Gloyna, of photosynthet lc I%8 oxygen product I on

Duckweed, Lemna minor --

50$ reduction In ch lorophy I I

58,320 Blackmen, et al. 1955

B-10

SPOCl4BS

Lymnaeld snal Is, Pseudosucclnea coiumel la )ossarla cubensls

24 hrs

Crayf Ish, Orccnectes proplnquus brconectes I mean Is Cambarus robusfus

48 hrs

Crayf Ish, Orconectes prop I nquus Orconectes Imunis TTambarus robustus

1 wk

Crayf I sh, o~rco~~t;,’ qropJIyus

Cambarus robustus

IO days

Crayfish, Orconectes prop I nquus Orconectes lrmnunis Cambarus robrstus

IO days

Rainbow trout, SaImD galrdneri

48 hrs

Rainbow trout, 24-day embryo Saimo galrdneri exposure

Ra I nbow trout, Saimo galrdnerl

24-day embryo exposure

Rainbow trout, Salmo galrdneri

Ra i nbow trout, Salmo qalrdneri

Table 5. Other data for 2,4-dichlwqhud

Result Ouration Effect (w/l)

FRESHWATER SPECtES

24-day embryo plus 4-day

larval exposure

24-day embryo plus 4-day

larval exposure

100% mortal I ty 10,000

lOO$ mortali

100% mortal I

tv 10,000

tY 5,ooo

145 mortal I ty 1,000

Increased blood glucose levels

1,000

ETC”

LC50 at hardness of 50 mg/l caCo3

LC50 at hardness of 200 lag/l caCo3

LC50 at hardness of 50 mg/l caCo3

LCSO at hardness of 200 mg/l CaCOJ

Reformwe

Batte & Swanson, 1952

TF3

Te ford, 1974

Telford, 1974

Tel ford, 1974

I Shunmay 6 Palensky, 1973

80 Blrge, et al. 1979

70 Blrge, et al. 1979

80 Birge, et al. 1979

70 Blrge, et al. 1979

B-11

Tablo 5. (Cant Inued)

Species

Goldfish, Carasslus auratus

Goldf Ish, Carass i us auratus

Goldf Ish, Carasslus auratus

Goldfish, Carassius auratus

Goldf Ish, Carass I us wratus

Fathead nlnnow f juveni le), Pfmephales promelas

Channel catf Ish, I eta lurus punctatus

Channel cstf Ish I eta lurus punctatus

Channel catfish, lctalurus punctatus

Channel cetf I sh, lctalurus punctatus

BluegIll, Lepomls wcrochlrus

Largewuth tnss, Hlcropterus salmoldes

Duratlcm

4-day embryo exposure

4-day emtryo exposure

4-day embryo p lus 4-day

larval exposure

4-day ecpbryo p lus 4-day

larval exposure

24 hrs

192 hrs

I-day embryo exposure

4-day eatryo exposure

4-day emb-yo plus 4-day

larval exposure

4-day eatwyo plus 4-day

larval exposure

48 IN-S

48 hrs ETC’

Ef feet

LC50 at hardness of 5Gmg/lCaCO3

LC50 at hardness of 200 rag/l caCo3

LC50 at hardness of 50 mg/l caCo3

LC50 at hardness of 200 109/i caCG3

LC50

LC50

LC50 at hardness of 50 mg/i caCO3

LC50 at hardness of 200 rig/l caco3

LC50 at hardness of 5Omg/lcaCo3

LC50 at hardness Of 200 mg/i caCG3

ETC.

Ruult his/l 1

1,760

Rof YYLU

8lrge, et al. 1979

1,240 Bfrge, et al. 1979

390 Blrge, et al. 1979

260 Blrge, et al. 1979

7,800

6,500

Kotmyashl, et al. 1979

Phlpps, et al. Manuscr I pt

1,850

1,700

1,350

1,070

14

0.4

Blrge, et al. 1979

Blrge, et al. 1979

Blrge, et al. 1979

Blrge, et al. 1979

;t$;ay & Palensky,

Shuvsy 6 Palensky, 1973

B-12

Table 5. Kontlnuedd)

Spec les ResuIt

Duration Effect (w/l) Ref eremce

SALTWATER SPECIES

Mountain bass** Acute Kuhlla sandvicensls response

Moderate react Ion

20,000 Hlatt, et al. 1953

l ETC = the highest estimated concentration of material that wit I not impair the flavor of the flesh of exposed f Ish.

**Endemic In tiawall

B-13

REFERENCES

Batte, E.G. and L.E. Swanson. 1952. Laboratory evaluation of organic com-

pounds as molluscicides and ovicides. II. Jour. Parasitol. 38 65.

Birge, W. J., et al. 1979. Toxicity of organic chemicals to embryo-larval

stages of fish. EPA-560/11-79-007. U.S. Environ. Prot. Agency.

Blackman, G.E., et al. 1955. The physiolgical activity of substituted

phenols. I. Relationships between chemical structure and physiological

activity. Arch. Biochem. Biophys. 54: 45.

Hiatt, R.W., et al. 1953. Effects of chemicals on a schooling fish, Kuhlia

sandvicensis. Biol. Bull. 104: 28

Holcombe, G.W., et al. Effects of phenol, 2,4-dimethylphenol, 2,4-dichlo-

rolphenol, and pentachlorophenol on embryo, larval, and early-juvenile fat-

head minnows (Pimephales promelas). (Manuscript)

Huang, J. and E.F. Gloyna. 1968. Effect of organic compounds on photo-

synthetic oxygenation. 1. Chlorophyll destruction and suppression of pho-

tosynthetic oxygen production. Water Res. 2: 347.

Kobayashio, K., et al. 1979. Relation between toxicity and accumulation of

various chlorophenols in goldfish. Bull. Jap. Sot. Sci. Fish. 45: 173.

B-14

Koppewnan, H.L., et al. 1974. Aaueous chlorination and ozonation studies.

I. Structure-toxicity correlations of phenolic compounds to Daphnia magna.

Chem. Biol. Interact. 9: 245.

Phipps, G.L., et al. The acute toxicity of phenol and substituted phenols

to the fathead minnow, (Manuscript)

Shumway, D.L. and J.R. Palensky. 1973. Impairment of the f lavor of fish by

water pollutants. EPA-R3-73-010. U.S. Environ. Prot. Agency

Telford, M. 1974. Blood glucose in crayfish. II. Variations induced by

artificial stress. Comp. Biochem. Physiol. 48A: 555.

U.S. EPA. 1978. In-depth studies on health and environmental impacts of

selected water pollutants. Contract No. 68-01-4646. U.S. Environ. Prot.

Agency.

B-15

Mammalian Toxicology and Human Health Effects

EXPOSURE

Ingestion from Water

Absorption of 2,4-dichlorophenol {herein referred to as 2,4-

DCP in this document) by biological tissues may occur upon exposure

to 2,4-DCP either dissolved in water or associated with suspended

matter or sediments in water. Chlorophenols such as 2,4-DCP are

weak acids that become increasingly ionized under alkaline condi-

tions; they are mainly non-ionized at physiological pH. These pro-

perties, together with the lipophilic nature of chlorophenols (in-

cluding 2,4-DCP), make it likely that chlorophenols would be ab-

sorbed from the gastrointestinal tract.

Sources of 2,4-DCP in water may be diffuse (e.g., agricultural

runoff) or localized (e.g., point source pollution from manufactur-

ing waste discharges). Sidwell (1971) verified the presence of

2,4-DCP in 2,4-dichlorophenoxyacetic acid (2,4-D) manufacturing

wastes. Over a 7-month period, total chlorophenol content ranged

from 68 mg/l of waste to a high of 125 mg/l, with 2,4-DCP content

ranging as high as 89 percent of the total. Details of these find-

ings are presented in Table 1.

If certain assumptions are made, the data of Sidwell (1971)

can be used to estimate human exposure to 2,4-DCP from drinking

water obtained below a point source of this type. Assuming (1) an

effluent with a 2,4-DCP concentration of 125 mg/l in water contain-

ing 100,000 mg/l of total solids (Table 1), (2) dilution in the

watercourse occurring to the point where an acceptable freshwater

total solids concentration of 1,000 mg/l is reached, and (3) no

removal of 2,4-DCP by water treatment, drinking water will contain

C-1

TABLE 1

Industrial Plant Effluent Content of Chlorophenolsa

Date Sampled 25 Jan 3 Mar 21 Apr 28 May 27 Aug

Total Solids (mg/l) 6,960 40,100 76,320 104,860 11,000

Temperature (°C) 12 18 21 28.5 24

PH 7.5 7.6 7.4 7.4 7.0

Chlorophenols (mg/l) 68 118 125 112 74

Phenol Type (3) b

Phenol- 3.4 6.2 1.7 24.8 trace

2-chloro- 2.9 6.1 trace trace trace

2,4-dichloro- 73.6 17.9 20.0 11.4 89.0

2,6-dichloro- 9.9 41.7 38.8 30.5 3.0

2,5-dichloro- trace 6.2 1.7 trace 1.8

4-chloro- 2.5 12.1 18.3 20.0 2.8

2,4,6-trichloro- 2.8 9.9 19.5 13.3 3.4

2,4,5-trichloro- 4.7 trace trace trace trace

aModified from Sidwell, 1971 b Percent of total phenols present

C-2

2,4-DCP at an estimated concentration of 1.25 mq/l. If the daily

water intake of a 70 kg person is assumed to be 2 liters, this would

result in a daily 2,4-DCP dosage of 0.036 mq/kq body weight/day.

It should be emphasized that this dosage is a worst case exposure

level that would probably occur only in drinking water obtained

below a 2,4-DCP-contaminated point source discharge.

Sharpee (1973) noted the presence of 2,4-DCP in soil treated

with 2,4-dichlorophenoxyacetic acid (2,4-D). This presence may be

accounted for by the photolytic or microbial breakdown of 2,4-D

which will be discussed later in this document. Walker (1961)

studied the contamination of ground water by the migration of waste

products from the manufacture of chemicals at the Rocky Yountain

Arsenal, Denver, Colorado. Walker reported the phytotoxic proper-

ties of water caused by either 2,4-D or an unnamed "closely related

compound." The 2,4-D type compounds were not a direct product of

the Arsenal operations, but rather were apparently the result of

chemical reactions which occurred within basins used for the stor-

age of effluents from a variety of Arsenal operations.

If diffuse or point source contamination of waters with 2,4-

DCP is in fact occurrinq, the dissipation of this compound in

aquatic environments becomes an important consideration. The major

avenues of 2,4-DCP dissipation that have been studied are microbial

degradation and photodecomposition. Aly and Faust (1964) examined

the dissipation of 2,4-DCP from natural lake waters at a buffered

pH of 7. In aerated lake waters, with initial 2,4-DCP concentra-

tions of 100, 500, and 1,000 uq/l, the percentages of 2,4-DCP re-

maining at 9 days were 0, 0.34, and 46 resoectively. By contrast,

initial concentrations of 100, 500, and 1,000 uq/l in unaerated and

c-3

unbuffered waters resulted in percentages of 40, 51.6, and 56,

respectively, remaining at 17 days. Aly and Faust concluded that

the persistence of chloroohenol would tend to increase at lower pH

and under anaerobic conditions that might result from the decompo-

sition of excessive organic matter.

Inqols, et al. (1966) studied the degradation of various chlo-

rophenols by activated sewage sludge and concluded that 2,4-DCP was

degraded more rapidly by activated systems with previous exposure

to chlorophenols than by those with no previous exposure to chloro-

phenols. When activated sludge was exposed to 2,4-r)CP at levels of

100 mq/l of sludge, 75 percent of the chemical disappeared in two

days, and essentially 100 percent was gone in five days. Yemmett

(1972) showed that microorganisms acclimated to the herbicide 2,4-D

could degrade 2,4-DCP without a lag period, implying similar bio-

logical pathways for the two compounds.

When 2,4-DCP was subjected to aeration basin treatment, the

initial concentration of 64 mq/l dropped to an undetectable level

within five days (Sidwell, 1971); this was more rapid than the rate

of degradation observed for 2,4-DCP in distilled water. When an

aerated lagoon alone was used, removal of all chloronhenols varied

from 55 to 89 percent. Overall, removal using both lagoon and sta-

bilization ponds ranged from 87 to 94 percent. Thus, natural

degradation of 2,4-dichlorophenol may be enhanced by proper appli-

cation of effluent waste management principles.

Dissipation of dichlorophenols also occurs through ohotode-

composition in aqueous solutions. Aly and Faust (1964) demonstrat-

ed that (1) 2,4-DCP was decomposed by ultraviolet light, and

C-4

(2) the rate of photolysis in distilled water decreased as pH de-

creased. Degradation of 50 percent of 2,4-DCP by ultraviolet light

was accomplished in two minutes at pH 9.0, in five minutes at pH

7.0, and in 34 minutes at pH 4.0. The studies of Aly and Faust were

conducted with light of wavelength 253.7 nm, which is slightly

shorter than the natural ultraviolet radiation wavelength range of

292 to 400 nm.

The riboflavin-sensitized dimerization of 2,4-dichlorophenol

to tetrachlorodiphenyl ethers, tetrachlorodihydroxy-biphenyls, and

other products was reported by Plimmer and Klingebiel (1971).

Chlorinated dibenzo-p-dioxins, which could have resulted from ring

closure of these tetrachlorodiphenyl ethers, were not detected in

the products of photolysis. The authors speculated that failure to

detect chlorinated dibenzo-p-dioxins may have been due to the rapid

photolytic breakdown of those dioxins. Rapid photolysis of chlori-

nated dibenzo-p-dioxins was confirmed by Crosby, et al. (1971).

That 2,4-dichlorophenol can be formed as a photolytic product

of the herbicides 2,4-D and nitrofen (2,4-dichlorophenyl p-nitro-

phenyl ether) in aqueous suspension under sunlight or simulated

sunlight, has been noted by several investigators, including Aly

and Faust (1964), Zepp, et al. (1975), and Nakaqawa and Crosby

(1974a,b). Crosby and Tutass (1966) irradiated 2,4-D with artifi-

cial light (254 nm) and natural sunlight and observed that under

both conditions 2,4-dichlorophenol was formed as a photolytic prod-

uct of 2,4-D and was further degraded to 4-chlorocatechol. 2,4-DCP

was photolabile, with 50 percent being lost in five minutes at

pH 7.0.

C-5

Microbial decomposition of 2,4-dichlorophenol in soils and

aquatic environments has been extensively studied. Alexander and

A’eem (1961) found that when 80 uq 2,4-DCP/ml medium was incubated

in the presence of Dunkirk silt loam and Mardin silt loam, 2,4-DCP

was not detectable after nine and five days, respectively. When

these soil preparations were treated with sodium azide, no disap-

pearance of 2,4-DCP was noted, supporting the role of microbioloqi-

cal processes in the degradation. Loos, et al. (1967) found that

extracts of Arthrobacter sp. contained enzymes capable of dehalo-

qenating 2,4-dichlorophenol. Degradation was rapid, with 100 per-

cent chloride release from 2,4-DCP occurring after four hours of

incubation. The cells responsible for the dehaloqenating process

were active when cultured on the herbicides 2,4-D or 2-methyl-4-

chlorophenoxyacetate (MCPA) . Kearney, et al. (1972) found no

tetrachlorodibenzo-p-dioxin in soils treated with up to 1,000 uq

2,4-DCP/q. Sharpee (1973) measured 2,4-DCP present in the soil as

a consequence of 2,4-D application and found that 2,4-DCP did

appear in soil treated with 2,4-D, but it did not persist as long as

the 2,4-D.

As indicated earlier, the principal source of 2,4-dichloro-

phenol in soils is believed to be the herbicide 2,4-D. The various

intermediates (including 2,4-DCP) in the microbial metabolism of

2,4-D have been characterized by several investigators (Spokes and

Walker, 1974; Loos, et al., 1967; Bollag, et al., 1968; Evans, et

al., 1971; Paris and Lewis, 1973; Ingols, et al., 1966; Alexander

and Aleem, 1961). Kearney and Kaufman (1972) have shown that the

organisms capable of degrading 2,4-D to 2,4-tX~ continue the deqra-

dation process to catechol intermediates and finally to succinic

acid. Thus, the herbicide 2,4-D is eventually biodeqraded to an

ecologically acceptable product, succinic acid.

Recently, attention has focused on a potential chlorophenol

source of a more ubiquitous nature than herbicide and pesticide

applications. Both municipal and industrial wastewater are often

subjected to chlorination to achieve disinfection and deodorization

(Barnhart and Campbell, 1972). One result of chlorination is the

reaction of chlorine with phenol to produce chlorophenols, some of

which are a source of obnoxious odors and/or taste (Dietz and

Traud, 1978; Barnhart and Campbell, 1972: Burttschell, et al.

1959; Hoak, 1957).

Phenol has been observed to be quite reactive with chlorine in

dilute aqueous solutions. This high reactivity of phenol is at-

tributed to the ring-activating, electron-releasing properties of

the -OH functional group (Barnhart and Campbell, 1972; Morris,

1978). Halogen substitution is favored in the ortho- and para-

positions (Burttschell, et al. 1959).

Chlorination of phenols results in a stepwise substitution of

the 2, 4, and 6 positions of the aromatic ring. Barnhart and Camp-

bell (1972) felt that it was probable that chlorination resulted in

a complex mixture of chlorophenols. Burttschell, et al. (1959)

chlorinated 1 liter of 20 mq phenol/ml solution containing 2 q/l

sodium bicarbonate with 40 mq chlorine and isolated 2,4-DCP as one

of three major chlorophenols. Relative chlorophenol content deter-

mined in this study was as follows:

c-7

Component Percent of Product

Phenol l-2 2-Chlorophenol 2-5 4-Chlorophenol 2-5 2,4-Dichlorophenol 20 2,6-Dichlorophenol 25 2,4,6-Trichlorophenol 40-50

(Absolute amounts of chlorophenols were not reported.)

Lee and Morris (1962) verified the stepwise chlorination of

phenol to chlorophenolic compounds. Furthermore, they determined

that the reaction rate and yield of 2,4-DCP is quite pH dependent,

with a decrease in generation time and an increase in yield for

2,4-DCP as pH increases from 7 to 9. The reactions occurred at ini-

tial chlorine concentrations of 1 uq/g and phenol concentrations of

50 nq/q.

Jolley (1973) indicated that development of chlorinated orqan-

its, including chlorinated phenols, is retarded in solutions with

high ammonia concentrations. In a later study, Jolley, et al.

(1978) examined the chlorination of sewage waters under conditions

simulating those used for disinfection of sewage effluents and/or

antifoulant treatment of cooling waters of electric power qenerat-

inq plants. Over 50 chloro-organic constituents were senarated in

each analysis of concentrated sewage effluent chlorinated in the

laboratory with 2.5 to 6 mq/l concentrations of chlorine. similar

studies were also done on two bodies of lake water, each receiving

effluent from a coal-fired, electric-power generating plant. Tn

the three systems examined, Jolley, et al. (1978) detected mono-

chlorophenols at nq/q levels but found no dichlorophenols.

C-8

Glaze, et al. (1978) identified trichlorophenols, but found no

dichlorophenols, in superchlorinated municipal wastewaters. Thus,

in contrast to laboratory demonstrations of DC? formation, recent

work under conditions simulating the natural environment has not

established that 2,4-~cP is a significant product resulting from

chlorination of phenol-containing waters.

Ingestion from Food

Any 2,4-dichlorophenol contamination of food products (non-

aquatic) would probably result from use of the herbicide 2,4-D. As

stated earlier, 2,4-DCP is a possible contaminant of 2,4-D, as well

as an intermediate compound in the biological and ohotolytic degra-

dations of 2,4-D.

Absorption of 2,4-DCP has been reported for some plant snecies

(Isensee and Jones, 1971). Total DCP content in oat and soybean

plants increased for approximately three weeks when the soil con-

tained a DCP concentration of 0.07 ug/g. As these plants grew, the

total tissue content of DCP remained relatively constant but de-

creased as the plants matured. At the time of harvest, oats con-

tained 0.01 uq of DCP per gram of plant tissue, and soybeans con-

tained 0.02 vg/g. The 2,4-DCP did not seem to concentrate in the

plant seeds. DCP was not detected in the grain of these oat plants,

and the soybean seeds contained only 1 to 2 percent of the total

plant DCP. MO evidence was found of DCP translocation in soybeans

after foliar application.

The conversion of 2,4-D to 2,4-DCP has been demonstrated in

sunflowers, corn, barley, strawberries, and kidney beans. Steen,

et al. (1974) found that 2,4-DCP residues in plants treated with

c- 9

2,4-D herbicide were from 20 to 100 times lower than residues of

2,4-D. Related studies by Sokolov, et al. (1974) involved applica-

tion of 2,4-D to rice fields. At harvest, rice grain contained

neither 2,4-D nor 2,4-DCP, even though 2,4-DCP was present in the

rice plant. The 2,4-DCP content in potato tubers treated with

2,4-D amounted to less than 10 percent of the total 2,4-D content.

There is little information on the transfer of 2,4-D or its

degradation compounds to food products of animal origin. Mitchell,

et al. (1946) provided evidence for the gastrointestinal absorotion

of 2,4-D in lactating dairy cows and detected the herbicide in

blood serum during a 106-day oral dosing study. However, 2,4-D was

not detected in the milk. Yore recently, 2,4-D was not found

(detection limit 0.1 pg/g) in bovine milk following oral doses of 5

ug 4-(2,4-dichlorophenoxybutyric) acid [4-(2,4-DB)] (Gutenmann, et

al. 1963a) or 2,4-D (Gutenmann, et al. 1963b) or 50 uq 2,4-n

(Bathe, et al. 1964a) per gram of feed.

Clark, et al. (1975) studied the tissue distribution of 2,4-

DCP in sheep and cattle fed 2,4-D at the relatively high concen-

trations of 300, 1,000, and 2,000 ug/g of feed. Given that the

daily ration is approximately 3 percent of the body weight, these

feed concentrations are equivalent to approximate dosages of 9, 30,

and 60 mg/kg body weight, respectively. The treated diets were fed

for 28 days, and resulting concentrations of 2,4-D and 2,4-DCP in

several edible tissues were determined (Table 2). With a detection

limit of 0.05 ug/g, analysis did not detect 2,4-DCP in the fat or

muscle of cattle and sheep, even at the highest dose levels. How-

ever, the kidney and liver were found to contain large amounts of

c-10

TABLE 2

2,4-D and 2,4-DCP Residues (in mg/kg) in Sheep and Cattle Fed 2,4-Da

Compound

2,4-D (Dose mg/kg body weight/day) Sheep Cattle

60 60b 9 30 60

2,4-D 2,4-DCP

2,4-D 2,4-DCP

2,4-D 2,4-DCP

2,4-D 9.17 0.37 2.53 8.67 10.9 2,4-DCP 0.26 0.07 0.56 1.17 1.06

0.06 (0.05

0.10 LO.05

0.98 0.29 < 0.05 0.14 9.23 0.16 0.15 0.11 0.59 0.31

Yuscle

(0.05 40.05 co.05 40.05

Fat

0.15 0.13 (0.05 (0.05

Liver

Kidney

40.05 co.05

0.45 co.05

0.07 < 0.05

0.34 co.05

aModified from Clark, et al. 1975 b Dosed 28 days, then withdrawn from 2,4-D for 7 days

C-L1

2,4-DCP proportional to the dose given. Furthermore, when sheep

were withdrawn from 2,4-D for one week, measurable amounts of 2,4-

DCP were still detected. Based on the limited evidence presented,

the liver appeared to retain 2,4-DCP for longer periods than did

the kidney. The data presented do not allow accurate calculation

of a depletion rate, nor can the total time period of measurable

residues be ascertained.

Sherman, et al. @ (1972) fed technical grade Nemacide [O-(2,4-

dichlorophenyl)-O,O-diethyl phosphorothioatel at 50, 100, 200, and

800 ug/g of feed to laying hens for 55 weeks. Analysis for 2,4-~0

(a metabolite of Nemacide Q by gas-liquid chromatography (detection

limit 0.006 to 0.208 uq/g) resulted in detection of 2,4-DCP resi-

dues in liver and yolk, but not in muscle or fat. Details of the

analytical findings are presented in Table 3. As in the studies of

Clark, et al. (1975) I there does appear to be some predilection of

2,4-DCP for liver, even when formed by biotransformation from two

parent compounds. In the hens studied, liver 2,4-DCP concentration

63 decreased as the dosage of Nemacide was decreased. The highest

mean liver level of 2,4-DCP found in hens was 0.56 ug/g, identical

to a mean level of 0.56 uq/g found in the kidneys of cattle fed 300

ug 2,4-D/g of feed (the dosage level that most closely approximates

possible field exposure) by Clark and coworkers (1975). It should

be noted that the Sherman study was strictly a laboratory study,

using conditions that are not likely to occur in the field. How-

e'ver , in a worst-case exposure situation, the consumption of 2,4-

DCP-contaminated chicken liver and cattle kidney could result in

approximately equivalent human exposure.

c-12

TABLE 3

Q 2,4-Dichlorophenol Residues in Laying Hens fed Nemacide

[O-(2,4-dichlorophenol)-0,0-diethyl phosphorothioatela

Nemacid P Feed Concentration

in ppm

Days since Withdrawal

Gil from Nemacide

Residues of 2,4-DCP (ppm) mean (and range)

Liver Egg Yolk

800 0 0.47(0.14-0.68) 0.61(0.34-0.75) 5 --- 0.27 7 0.50(0.25-0.75)

10 --- < 0.12 14 0.27(0.06-0.48) 21 0.19(0.11-0.27)

200

100

0 0.38(0.31-0.44) 0.15(0.12-0.17) 7 0.30(0.24-0.35)

14 0.14(0.10-0.18) 21 0.36(0.07-0.64)

0 0.26(0.25-0.26) 0.15(<0.1.2-0.21) 7 0.56

14 0.15(<0.05-0.33) 21 0.05

50 0 0.31(0.16-0.46) (0.12 7 0.18(0.14-0.22)

14 0.06((0.05-0.1.1) 21 0.05

aModified from Sherman, et al. 1972

c-13

Bjerke, et al. (1972) dosed dairy cows for three weeks with

2,4-D concentrations as high as 1,000 mg/kg of diet. 2,4-DCP was

not found in the milk or cream of treated cows.

The results of Clark, et al. (1975) can be used to calculate a

worst case estimate for the degree of human exoosure to 2,4-DCP

from consumption of contaminated meat. Assuming (1) an averaqe

forage yield of two tons (1,818 kg) per acre, (2) the retention of

all herbicide on the treated plants, (3) an application rate of 1

lb (454 gms) of 2,4-D per acre, and (4) consumption by an animal of

3 percent of its body weight per day in forage, then the dosage

delivered to an animal eating forage contaminated with this level

of 2,4-D would be approximately 7 mg 2,4-DCP/kg body weight. This

amount corresponds roughly to the lowest dosage (9 mg/kq body

weight) that was administered to cattle and sheep by Clark and his

colleagues. Based on the results of Clark, et al., it is reason-

able to expect that cattle fed a constant diet of forage contami-

nated with 2,4-D applied at commercial rates would accumulate 2,4-

DCP concentrations of approximately 0.11 pg/g of liver and 0.56

pg/g of kidney.

If a 70 kg person consumed 0.5 kg of kidney daily at a 2,4-W?

residue concentration of 560 vg/kg, that person would be consuming

approximately 280 ug of 2,4-DCP, or 4.0 uq/kq body weiqht, daily.

If that person also ingested 36 ug 2,4-DCP/kg body weight/day in

contaminated drinking water, as calculated from 2,4-DCP levels in

water downstream from a 2,4-DCP manufacturing plant (see Inqestion

from Water section), the resultant daily 2,4-dichlorophenol dosaqes

would total 40 pg/kg. It is therefore clear that the water would

c-14

contribute 90 percent of this highest calculated daily dosage of

2,4-DCP.

It should be emphasized that an exposure level of 4 ug 2,4-

DCP/kg body weight/day is a worst case example for food intake. It

would only occur if a person (1) ate 0.5 kg of kidney per day and

(2) all the kidney consumed was contaminated with 0.11 ug 2,4-

DCP/g. This contamination level would Drobably occur only if the

cattle were fed a constant diet of 2,4-D-sprayed forage, since

experimental evidence (Clark, et al. 1975; Xielinski and Fishbein,

1967) indicates that levels of 2,4-DCP in animal tissue diminish

rapidly following withdrawal of 2,4-D from the diet.

A bioconcentration factor (BCF) relates the concentration of a

chemical in aquatic animals to the concentration in the water in

which they live. The steady-state BCFs for a lipid-soluble com-

pound in the tissues of various aquatic animals seem to be prooor-

tional to the percent lipid in the tissue. Thus, the per capita

ingestion of a lipid-soluble chemical can be estimated from the per

capita consumptions of fish and shellfish, the weighted average

percent lipids of consumed fish and shellfish, and a steady-state

BCF for the chemical.

Data from a recent survey on fish and shellfish consumption in

the United States were analyzed by SRI International (U.S. EPA,

1980). These data were used to estimate that the per caoita con-

sumption of freshwater and estuarine fish and shellfish in the

United States is 6.5 g/day (Stephan, 1980). In addition, these

data were used with data on the fat content of the edible portion

of the same species to estimate that the weiqhted average percent

c-15

lipids for consumed freshwater and estuarine fish and shellfi.sh

is 3.0.

No measured steady-state bioconcentration factor is available

for 2,4-dichlorophenol, but the equation "Log BCF = (0.85 Log P) -

0.70" (Veith, et al. 1979) can be used to estimate from the octa-

nol-water partition coefficient (P) the BCF for aquatic orqanisms

that contain about 7.6 percent lipids (Veith, 1980). Based on an

average log P value of 3.19 (Hansch and Leo, 1979), the steady-

state bioconcentration factor for 2,4-dichlorophenol is estimated

to be 103. An adjustment factor of 3.0/7.6 = 0.395 can be used to

adjust the estimated BCF from the 7.6 percent lipids on which the

equation is based to the 3.0 percent lipids that is the weighted

average for consumed fish and shellfish. Thus, the weiqhted aver-

age bioconcentration factor for 2,4-dichloroohenol and the edible

portion of all freshwater and estuarine asuatic organisms consumed

by Americans is calculated to be 103 x 0.395 = 40.7.

Inhalation

There is no direct evidence to indicate that humans are ex-

posed to significant amounts of 2,4-DCP through inhalation. Al-

though the compound is volatile, no quantitative studies of inhala-

tion exposure or general environmental contamination have been

found.

Dermal

Dermal exposure to 2,4-DCP would most likely occur during the

manufacture, transport, or handling of the compound. Due to its

lipophilic nature and low degree of ionization at physioloqic DH,

absorption of 2,4-DCP would be expected; however, no data relating

to dermal absorption have been found.

C-16

PHARMACOKINETICS

Absorption

No information concernina the direct absorption of 2,4-dichlo-

rophenol in humans or animals was found. Toxicity data to be

developed later confirm the existence of systemic toxicosis, indi-

cating that 2,4-DCP is absorbed by several routes.

Because of their high lipid solubility and low ionization at

physiological pH, dichlorophenols would be expected to be readily

absorbed following ingestion.

Distribution

No information was found concerning distribution of 2,4-DCP in

man. The previously discussed (see Inqestion from Food section)

animal studies (Clark, et al. 1975; Sherman, et al. 1972) demon-

strated distribution of 2,4-DCP in liver, kidney, and egg (see

Tables 2 and 3).

Metabolism

The biotransformation of 2,4-DCP in humans has not been re-

ported. No information could be found concerning the metabolism of

~,~-DCP administered directly to exoerimental animals. However, a

limited amount of information on the metabolism of 2,4-DCP derived

from administration of gamma and beta benzene hexachloride (BHC) to

mice was reported by Kurihara (1975). Mice were given Cl'-labeled

gamma- or beta-BHC by intraperitoneal injection, and the apoearance

of metabolites in the urine was monitored. 2,4-DCP and 2,4-DCP

conjugates were found and identified primarily as qlucuronides and

sulfates (Table 4). Administration of gamma-BHC resulted in a

majority of the 2,4-DCP beinq conjugated as the alucuronide, while

beta-BHC administration resulted in a greater amount of sulfate

c-17

TABLE 4

Urinary 2,4-DCP Metabolites of Benzene Hexachloride in Micea

Form of 2,4-DCP

BHC Isomer Glucuronide Sulfate Total

gamma-BHC

beta-BHC

4-5%b O-L% 4-6%

l-2% 3% 4-S%

aSource: Kurihara, 1975 b Percent of total metabolites

conjugate. Assuming that the mouse biotransforms 2,4-~Cp resulting

from endogenous metabolism in a manner similar to 2,4-DCP directly

administered, then sulfate and qlucuronide coniugation appear to be

major metabolic pathways.

Excretion

2,4-D has been found to be rapidly excreted in the urine of

mice (Zielinski and Fishbein, 19671, rats (Khanna and Fang, 1966),

sheep (Clark, et al. 1964), and swine (Erne, 1966a,b) under various

dosing conditions. The phenoxy herbicide WPA was also rapidly

excreted in cattle urine (Bache, et al. 1964b). However, excretion

data from studies using 2,4-DCP are not extensive, and no infor-

mation was found for 2,4-DCP excretion in man.

Karapally, et al. (1973) found that when rabbits were given

radioactive gamma-BHC, 2.5 percent of total radioactivitv in the

urine was due to 2,4-DCP. Data presented did not allow for deter-

mination of body burden or half-life. Shafik, et al. (1973) admin-

istered a daily dose of Nemacid @ in peanut oil orally to rats for

three days. Q After administration of 1.6 mg Nemacide , 67 percent

of that compound appeared in urine as 2,4-DCP within three days.

@ With a dosage of 0.16 mg Nemacide , 70 oercent of the pesticide

appeared as 2,4-DCP within 24 hours. Work cited earlier (Kurihara,

1975) indicated the appearance of metabolites of 2,4-DCP in urine

as a result of gamma- and beta-BHC administration (see Table 4).

EFFECTS

Acute, Subacute, and Chronic Toxicity

Farquharson, et al. (1958) indicated that the toxicity of

chlorophenols tends to increase as chlorination is increased.

c-19

The mechanism of toxic action for 2,4-DCP in mammalian systems

in vivo has not been well defined. Limited in vitro studies indi- -- --

cate two potential actions. 2,4-DCP inhibits ox.idative phosphoryl-

ation in rat liver mitochondria and rat brain homogenates (Farqu-

harson, et al. 1958; Mitsuda, et al. 1963). According to Mitsuda,

et al. (1963) n inhibitory activity of chlorophenols was roughly

correlated with the dissociation constant of the inhibitor. In

addition, chlorine atoms on the ortho position weakened the activ-

ity of mono- and dichlorophenols as oxidative inhibitors. A con-

centration of 4.2 x 10" M 2,4-~Cp inhibited oxidative phosphoryla-

tion by 50 percent in rat liver mitochondria. By comparison, pen-

tachlorophenol was approximately 40 times more active, and dinitro-

phenol was twice as active in inhibiting oxidative phosohorylation.

Stockdale and Selwyn (1971) reported observations suggesting

that the phenol-induced mediation of the passage of protons across

the inner mitochondrial membrane is sufficient to cause uncoupling

of oxidative phosphorylation. They further noted that phenols have

direct effects on the enzyme ATPase as well as on one or more compo-

nents of the electron transport system: however, neither of these

effects is actually involved in the uncoupling process.

Farquharson, et al. (1958) offered the conclusion that chloro-

phenols with pK values of 7.85 or less appear to be acutely associ-

ated with production of marked hypotonia and early onset of rigor

mortis after death. Similar clinical effects are associated with

well known oxidative uncouplers, such as 2,4-dinitrophenol and pen-

tachlorophenol. Relatively few studies of the acute or subacute

toxicity of 2,4-DCP have been reported. The acute LDsO values

determined by several investigators are presented in Table 5.

c-20

TABLE 5

Acute Mammalian Toxicity of 2,4-DCP

Species Route of Administration LD50

(w/kg 1 Reference

Rat Oral 580 Deichmann, 1943

Subcutaneous Deichmann, 1943

Rat Intraperitoneal 430 Farquharson, et al. 1958

Rat

Mouse

Oral

Oral

4,000 Kobayashi, et al. 1972

1,600 Kobayashi, et al. 1972

c-21

In the study by Farquharson, et al. (1958), acute poisoning of

rats following intraperitoneal 2,4-DCP injection appeared to be

characterized by the onset of hypotonia two to three minutes after

dosing. This effect began in the hindlimbs and moved forward until

the rats were prostrate. Eye reflexes were weakened and there was

no withdrawal from toe pinch. Muscle twitches rarely occurred

spontaneously and could not be evoked by auditory or tactile stimu-

li. Rectal temperature was only slightly decreased. Initial dose-

induced polypnea was followed by slowed respiration and dyspnea

as coma ensued. Rigor mortis appeared earlier in rats killed with

2,4-DCP than in control rats killed with ether,

The oral LDSO derived by Deichmann (1943) appears at odds with

the findings of Kobayashi, et al. (1972). Deichmann used fuel oil

as a solvent, which may have enhanced rapid uptake of 2,4-DCP. The

vehicle for the Kobayashi studies could not be determined. None-

theless, from the LD5* values, it appears that 2,4-DCP would con-

stitute an acute hazard only following massive exposure.

In a subacute (lo-day) study, Kobayashi, et al. (1972) found

that all mice survived when 2,4-DCP at 667 mg/kg body weight was

given orally. They derived LD50 figures for this study which ap-

pear similar to those listed for the acute studies (see Table 5).

In the same study (Kobayashi, et al. 1972), male mice were also fed

2,4-DCP in the diet over a 6-month beriod. Parameters evaluated

included average body weight, food consumption, orqan weight, glu-

tamic oxaloacetate transaminase, qlutamic pyruvic transaminase,

erythrocyte counts, leucocyte counts, and histopathological

changes. The estimated dose levels were 45 mg/kq/day, 100 mq/kg/

c-22

day, and 230 mg/kg/day, corresponding to dietary 2,4-DCP concentra-

tions of 5OC, 1,000, and 2,000 ug/g, respectively. No adverse

effects were noted in mice at any dose level, except for some

microscopic .non-specific liver changes after the maximum dose.

These changes included infiltration of round cells and swelling of

hepatocytes, with some differences in cell size. Two animals were

reported to have "dark cells" in the liver. (To the author's

knowledge, this term is not commonly used in the United States, and

its meaning is not clear.) Kobayashi, et al. concluded that 100

mg/kg/day is a maximum no-effect level in mice.

No other chronic toxicity studies using 2,4-dichloroohenol

have been found. One report in the literature (Bleiberg, et al.

1964) has suggested a possible role of 2,4-X? in acquired chlor-

acne and porphyria in workers manufacturing 2,4-DCP and 2,4,5-tri-

chlorophenol (2,4,5-TCP). The workers involved were also exposed

to acetic acid, phenol, monochloroacetic acid, and sodium hydrox-

ide. since various dioxins (including 2,3,7,8-tetrachloro-diben-

zo-p-dioxin (TCDD), which has been associated with chloracne) have

been implicated as contaminants of 2,4,5-TCP, the role of 2,4-r)CP

in inducing chloracne and porphyria is not conclusive (Huff and

Wassom, 1974).

Synergism and/or Antagonism

Reports of studies directly assessing the synergism or antago-

nism of 2,4-dichlorophenol by other compounds were not found.

Since 2,4-DCP is an uncoupler of oxidative phos?horylation (Mit-

suda, et al. 1963), it may be expected that concomitant exposure

to other uncouplers (e.g., pentachlorophenol, dinitrophenol) would

C-23

enhance that effect. In addition, exposure to gamma- or beta-RHC,

2,4-D, and nitrofen could add slightly to any primary body burden

of 2,4-DCP.

Any agent causinq liver damaqe sufficient to decrease the con-

jugation of 2,4-DCP with glucuronide or sulfate could conceivably

alter the excretion and/or toxicity of the oarent compound. How-

ever, there are no specific studies to reflect such an effect.

Teratoqenicity

Pertinent data could not be located in the available litera-

ture concerning the teratogenicity of 2,4-DCP.

Yutagenicity

p;Jo studies were found which addressed the mutaqenicitv of 2,4-

dichlorophenol in mammalian systems. Amer and Ali (1968, 1969) did

report some effects of 2,4-DCP on mitosis and meiosis in flower

buds and root cells of vetch (Vicia faba). Changes included meiot- --

ic alterations of chromosome stickiness, laqginq chromosomes, and

anaDhase bridqes when flower buds were sprayed with 0.1 M 2,4-DCP.

Yitotic changes of chromosome stickiness, laqqing chromosomes, dis-

integration, bridging, disturbed probhase and metaphase, and occa-

sional cytomyxis were seen in root cells exposed to 62.5 mg/l DCP.

Later studies (Amer and Ali, 1974) further confirmed the effect of

chromosome stickiness, lagging chromosomes, and fraqmentation in

35-day-old Vicia faba. -- The relationship of these changes to alter-

ations in mammalian cells has not been established.

Carcinoqenicity

Repeated application of phenol and some substituted Dhenols

has demonstrated promoting, as well as complete, tumorigenic activ-

C-24

ity (Boutwell and Bosch, 1959). In the Boutwell and Bosch study,

two trials included evaluation of 2,4-DCP as a promoter. In one

trial, 25 ~1 of a 20 percent solution of 2,4-~Cp in benzene was

applied twice weekly for 15 weeks to female Sutter mice two to

three months of age. The other trial was identical, except that

2,4-DCP was applied for 24 weeks. Application in both trials fol-

lowed an initiating dose of 0.3 oercent dimethyl-benzanthracene

(DMBA) in benzene.

The 2,4-DCP dose used corresponds to 5 mq of compound per

mouse at each application, or 10 mg/week when applied twice weekly.

Sutter mice two to three months old would be expected to weiqh 35

grams, so that the dose rate would be 40.82 mg/kg body weight.

Tumorigenic response was measured as follows:

1) The percentage of surviving mice bearing one or more papilloma was ascertained.

2) The number of papillomas on all survivinq mice was totaled and divided by the number of survivors to give the average number of papillomas per survivinq mouse.

3) The number of mice bearinq malignant tumors was determined.

Results of the promoter trial with 2,4-DCP are presented in

Table 6. Related promoter experiments with phenol and the two ben-

zene controls are included for comparative purposes. Soutwell and

Bosch concluded that the promoting activity of 2,4-DCP is similar

to that of phenol. However, no statistical analyses nor dose-

response data were included to support this comparison.

To see if there was a statistically significant difference

between the 2,4-DCP-treated mice and the benzene controls, a Fisher

C-25

TABLE 6

Appearance oE Skin Tumors in Mice Treated Cutaneously with Phenols following

a Cutaneous Dose OF 0.31 Dimethyl-benzanthracene (DtlBA) in Acetonea

b Treatments

Benzene control

Benzene control

109 phenol in benzene in DMBA

209 phenol in acetone

209 phenol in benzene

209 2,4-DCP in benzene

20% 2.4-DCP in benzene

Tine Animals No. of Mice Survivors Average Survivora with Examined

(week) (survivors/total) wl th Papi llo~s PapiIloras Epithelial Carcinomas (a) per Survivor 0)

15 15/20 7 0.07 a

24 27/32 11 0.15 0

20 24/3Q 33 0.62 13

12 21/24 58 5

24 10/33 100 3.20 20

15 27/33 48 1.07 11

24 16/23 75 1.62 6

‘Source: Modified from Boutwell and Bosch, 1959 b All received DMBA except where stated

C-26

exact test was undertaken for this document. Tumor incidence was

derived with the assumption that only survivors were examined for

tumors. The calculated results are presented in Table 7.

This analysis indicates that (1) the higher incidence of

papillomas in both 2,4-DCP-treated groups was not attributable to

chance, and (2) the carcinoma incidence was not significantly ele-

vated over controls.

This statistical exercise should not obscure a number of con-

siderations that could affect the meaningfulness of the results.

(1) The study used dermal application of a phenolic compound at 20

percent concentration in organic solvents. This concentration is

high enough to destroy hair follicles and sebaceous glands. The

papillomatous response observed may have developed in response to

chemical and/or physical damage from application of an irritant

compound. (2) Even with the harsh treatment, no malignant neo-

plasia was observed, except when DMBA was used as an initiator.

The only neoplasia observed was at the site of direct application.

(3) Pathological identification of benign and malignant tumors was

done on a gross level, with only periodic confirmation by micro-

scopic examination. (4) The mice were housed in creosote-treated

wooden cages, which themselves were capable of initiating a carci-

nogenic response.

The report of Boutwell and Bosch (1959) is the only one found

that deals with the tumorigenicity of 2,4-DCP. However, since the

study was designed primarily to detect promoting activity, the

effect of 2,4-DCP as a primary carcinogen is not well defined.

C-27

TABLE 7

Results of Fisher Exact Test Applied to Data from Routwell and Bosch (1959)

Treatment Duration of Incidence of P-value Incidence of P-value Treatment (wks) Papillomas CoZol

Epithelial vs. Carcinoma Control

Benzene control (I) 15 l/15 o/15

20% 2,4-DCP in benzene 15 13/27 0.61 x 1O-2 3/27 0.2548

Benzene control (II) 24 3/27 O/27

20% 2,4-DCP in benzene 24 12/16 0.36 x 1O-4 l/16 0.3721

C-28

The route of administration is not appropriate to the model

for carcinogenic risk assessment and has no established celation-

ship to oral exposure. Overall, the study does present evidence

that 2,4-DCP may be a possible promotor,

cable to evaluating the hazard of skin

2,4-DCP, alone or concurrent with other

Other Effects

and the work may be appli-

or respiratory exposure to

chemicals.

An odor threshold for 2,4-DCP in water has been reported by at

least three investigators. Hoak (1957) determined the odor thresh-

old of 2,4-DCP to be 0.65 ug/l at 30°C and 6.5 pg/l at 60°C. Deter-

mination of the detectable odor was made by a panel of two or four

people comparing flasks of test water to a flask of odor-free

water. The lowest concentration detected by any panel member was

taken as the odor threshold. Hoak speculated that odor should

become more noticeable as temperature increases; however, in evalu-

ating a series of chlorophenols and cresols, it was found that some

compounds had higher odor thresholds at 30°C, and others were high-

er at 6OOC.

Burttschell, et al. (1959) made dilutions of chlorophenol in

carbon-filtered tap water and used a panel of four to six people to

evaluate odor. Tests were carried out at room temperature, which

the investigator estimated to be 25'C. If a panel member's re-

sponse was doubtful, the sample was considered negative. The geo-

metric mean of the panel responses was used as the odor threshold.

For 2,4-DCP the threshold was 2 ug/l.

Diet2 and Traud (1978) used a panel composed of 9 to 12

persons of both sexes and various age groups to test the organolep-

c-29

tic detection thresholds for 126 phenolic compounds. To test for

odor thresholds, 200 ml samples of the different test concentra-

tions were placed in stoppered odor-free glass bottles, shaken for

approximately five minutes, and sniffed at room temperature (20-

22OC). For each test, water without the phenolic additive was used

as a background sample. The odor tests took place in several indi-

vidual rooms in which phenols and other substances with intense

odors had not been used previously. Geometric mean values were

used to determine threshold levels. To determine taste threshold

concentrations of selected phenolic compounds, a panel of four test

individuals tested water samples containing various amounts of ohe-

nolic additives. As a point of comparison, water without phenolic

additives was tasted first. Samples with increasing phenolic con-

centrations were then tested. Between samples, the mouth was

rinsed with the comparison water and the test person ate several

bites of dry white bread to "neutralize" the taste. Geometric mean

detection level values for both tests provided threshold levels of

0.3 pg/l for taste and 40 pg/l for odor for 2,4-DCP.

None of these three studies, however, indicated whether the

determined threshold levels made the water undesirable or unfit for

consumption.

c-30

CRITERION FORMULATION

Existing Guidelines and Standards

Presently, no standard for exposure to 2,4-X? in drinking or

ambient water has been set, although a standard of 0.1 mg/l

2,4-D, a related compound, has been set fNationa1 Academy of

ences (NAS), 19771.

Current Levels of Exposure

for

Sci-

Human exposure to 2,4-DCP has not been monitored, but a worst

case estimate of 40 ug 2,4-DCP/kg body weight/day of exposure was

presented in the Ingestion from Food section.

Special Groups at Risk

The only group expected to be at risk from hiqh exnosure to

2,4-DCP is industrial workers involved in the manufacturing or

handling of 2,4-DCP and 2,4-D. No data were found to relate expo-

sure or body burden to conditions of contact with 2,4-DCP.

Basis and Derivation of Criterion

Insufficient data exist to indicate that 2,4-n?? is a carcino-

genic agent. The only study performed (Boutwell and Bosch, 1959)

was designed to detect promoting activity, and the effect of 2,4-

DCP as a primary carcinogen could not be evaluated. Also, the

route of administration (dermal) in this study is inaporonriate for

use in the linear model for carcinogenic risk assessment (see Car-

cinogenicity section).

Minimal health effects data exist on the acute and chronic

effects of 2,4-DCP. Only one study of a chronic nature (Kobayashi,

et al. 1972) was found. Kobayashi and colleagues determined a

chronic (6-month) no-effect level for 2,4-DCP to be 1,000 ug/q of

diet for mice, which was equivalent to 100 mg/kq body weight/dav.

c-31

An equivalent daily dose for a 70 kg adult human would be 7,000

mg/day (100 mg/kg/day x 70 kg). Applying an uncertainty factor of

1,000 as suggested by the National Academy of Sciences Safe Drink-

ing Water Committee (1977), the Acceptable Daily Intake (ADI) for a

70 kg adult human would be 7,000 mg f 1,000 = 7 mg. Solving the

equation (2L)(C) + (C)(%CF) (fish consumption/day) = ADI, the water

quality criterion (C) can be computed:

(2L)(C) + (C)(40.7)(0.0065) = 7 mg

(2L)(C) f (C) (0.26455) = 7 mg

c = 7 mg 2.26455L

c = 3.09 mg/l

where:

7 mg = the calculated daily exposure for a 70 ks nerson (ADI) based on the above conditions

2L = amount of drinking water consumed/day

0.0065 kg = amount of fish consumed/day

C = maximum permissible level in water based on above conditions

Thus, a criterion level based entirely upon toxicological data

would be 3.09 mg/l.

Human health is a subjective measurement in many respects.

The organoleptic properties of 2,4-DCP could conceivably alter

human health by causing a decrease in water consumption. This

might be of particular importance to individuals with certain renal

diseases or in instances where dehydration occurs as a result of

vigorous exercise, manual labor, or hot weather.

C-32

Since the odor and taste detection threshold concentrations

for 2,4-dichlorophenol are well below any toxicity-based criterion

level that may be derived, the ambient water quality criterion is

based on organoleptic data. It should be emphasized that this cri-

terion is based on aesthetic qualities rather than health effects.

However, to the effect that this criterion is below the level de-

rived from the chronic toxicity study of Kobayashi, et al. (19721,

it is likely to also be protective of human health.

The data of Hoak (1957), Burttschell, et al. (1959), and Diet2

and Traud (1978) all indicated that low microgram concentrations of

2,4-dichlorophenol in water are capable of producinq a discernable

odor. Dietz and Traud further observed a distinct flavor altera-

tion of water at sub-microgram levels of 2,4-DCP. The Burttschell,

et al. (1959) and Diet2 and Traud (1978) studies did not indicate a

range of responses: however, because of the variability of respons-

es inherent in such procedures, it is certainly possible that the

odor threshold for some evaluators (at least in the Burttschell

group) would extend downward toward the 0.65 ug/l figure of Hoak.

Thus, the data from these three studies are considered to be rea-

sonably mutually supportive (i.e., Hoak's 0.65 ug/l for odor,

Burttschell's 2.0 ug/l geometric mean value for odor, and Dietz and

Traud's geometric mean values of 40 pg/l for odor and 0.3 pg/l for

taste).

Therefore, based on the prevention of undesirable orqanoleptic

qualities, the criterion level for 2,4-dichlorophenol in water is

0.3 !Jg/l. This level should be low enough to prevent detection of

objectionable organoleptic characteristics and far below minimal

c-33

no-effect concentrations determined in laboratory animals. As more

substantive and reliable data become available in the future, a

criterion level based on human health effects mav be more confi-

dently postulated.

It should be emphasized that data are needed in the followinq

areas to

1)

2)

3)

4)

5)

properly evaluate any hazard from 2,4-DCP:

Yonitoring of worker exposure to 2,4-DCP in indus- tries manufacturing or using the chemical.

Monitoring of Dublic water supplies and industrial and municipal effluents to determine an expected range of concentrations under differinq environ- mental conditions.

Yore definitive studies of residue kinetics of 2,4- DCP in food animals which are exposed to products capable of generating 2,4-DCP.

Evaluation of chronic toxicity, mutaqenicity, and teratogenicity of 2,4-DCP using currently accept- able techniques.

A carcinoqenicity study of 2,4-DCP usinq the oral route and evaluated according to current protocols.

C-34

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C-36

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